Apparatus and methods for improving health outcomes of preterm infants

ABSTRACT

Adverse effects of pain in a premature infant, especially a very or extremely premature infant may be ameliorated by exposing the infant to stimuli comprising one or more of vertical oscillating motion simulating breathing, skin contact with an interface that mimics human skin and exposure to sounds and/or vibrations that simulate heartbeats. A device including a movable platform provides such stimuli within a neonatal intensive care incubator. The device provides simulated maternal breathing through vertical movement at a rate and speed similar to that experienced by an infant lying upon its mother&#39;s chest. It further provides simulated maternal skin interface feel as well as heartbeat sound. These simulated sensory parameters appear to have an innate calming effect upon a preterm infant that reduces the duration and severity of the infant&#39;s response to a pain event. The same stimulations may reduce occurrence of below-baseline fluctuations of brain blood oxygen content.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. application Ser. No.15/516287, which is a 371 of PCT International Application No.PCT/CA2015/051002 filed 2 Oct. 2015. PCT/CA2015/051002 claims priorityfrom U.S. Application No. 62/059274 filed 3 Oct. 2014 and also U.S.Application No. 62/203071 filed 10 Aug. 2015. For purposes of the UnitedStates, this application claims the benefit under 35 U.S.C. § 119 ofU.S. Application No. 62/059274 filed 3 Oct. 2014 and entitled PAINTHERAPY METHOD AND DEVICE FOR PRETERM INFANTS and U.S. Application No.62/203071 entitled BRAIN BLOOD OXYGEN STABILIZATION METHOD AND DEVICEFOR PRETERM INFANTS filed 10 Aug. 2015, both of which are herebyincorporated herein by reference for all purposes.

BACKGROUND

The normal term of a human pregnancy is in the range of 37 to 42 weekswith 40 weeks being typical. Infants born more than 3 weeks before fullterm (i.e. at less than 37 weeks of gestation) are called ‘premature’.

Approximately one of every eight infants born in the United States ispremature. Premature infants tend to be underweight in comparison tofull term infants. Premature infants also tend to suffer from varioushealth problems. These health problems can be very complicated. Suchhealth problems may stem from the fact that a premature baby's organsmay not yet have developed to the point that the baby can liveindependently outside of the womb. For example, premature infants oftenhave difficulty breathing and regulating their body temperatures and mayhave other problems caused by underdevelopment of a range of organs.These problems particularly affect infants born before 35 weeksgestational age. All biological systems in such infants are immaturehaving been previously regulated through the mother's placenta.

Critical biological systems that can be underdeveloped in prematureinfants include:

-   -   the central nervous system (e.g. brain)    -   the cardiovascular system,    -   the immune system and    -   the gastro-intestinal system.

The health problems faced by premature infants tend to vary dependingupon how prematurely the infants are born. Infants born in the laterpreterm (i.e. between 35 and 37 weeks gestation) may look like full termbabies. However, even late preterm babies tend to be at greater risk forcertain health problems than full term babies.

Infants born at or before 34 weeks of gestation typically lack theability to suck and swallow in a coordinated manner.

Infants born between 32 and 34 weeks of gestation may be called‘moderately preterm’. Infants born at less than 32 weeks of gestationmay be called ‘very preterm’. Infants born at or before 28 weeks ofgestation may be called ‘extremely preterm’.

Infants weighing less than 1500 grams and/or being eight weeks or morepremature (i.e. very or extremely premature infants having gestation of32 weeks or less), can be exceedingly frail and usually require supportto stay alive and grow. With their immature biological systems, theseinfants cannot breathe on their own to maintain normal oxygen levels,regulate their body temperatures, fight infections effectively or feedadequately.

Premature infants are typically held in a neonatal intensive care unit(NICU) where their health may be carefully monitored. Monitoringpremature infants often includes blood tests (e.g. to check glucose,oxygen, and bilirubin levels); chest X-rays, and continuouscardiorespiratory monitoring.

Premature infants are often placed in incubators or “isolettes” in whichair temperature is controlled. Many incubators also include systems forcontrolling humidity of the air inside the incubator. Some incubatorsalso include facilities for controlling oxygen content of the air insidethe incubator.

An incubator in a NICU may, for example, provide:

-   -   delivery of ambient oxygen to help maintain oxygen levels;    -   a relatively closed volume to exclude environmental        dust/pollutants which can cause lung damage;    -   systems for controlling temperature to help maintain body        temperature;    -   systems for maintaining and controlling humidity to prevent skin        breakdown which is linked to increased risk of infection;    -   a relatively sterile space to help prevent infection; and/or    -   attenuation of some ambient light and noise to allow the infant        to rest.

It is challenging to assess whether premature infants are experiencingpain or stress because they may not respond to pain in the ways typicalof full-term infants. Some caregivers may take the lack of ‘normal’response to painful stimuli to indicate that premature infants are notbothered by pain. The inventors consider that this is a particularproblem that is made worse by the fact that premature infants aresubjected to frequent procedures that can be painful such as heel pricksto obtain blood for testing. Such painful stimuli cause stress topremature infants. While such stress can adversely affect the infants,the procedures are necessary and it is not generally practical tocontrol this type of pain in premature infants using analgesic drugs.The inventors believe that methods and apparatus that may be used toreduce stress in premature infants may improve health outcomes for thoseinfants.

There remains a need for effective techniques for improving healthoutcomes for premature infants, especially ‘very’ and ‘extremely’premature infants.

SUMMARY

The present invention has a number of aspects. Without limitation, theseaspects include:

-   -   apparatus useful in the care of pre-term infants;    -   uses of such apparatus in the care of pre-term infants;    -   methods for treating preterm infants;    -   methods for controlling pain in preterm infants; and    -   methods for reducing sub-baseline brain blood oxygen content in        preterm infants.

While various aspects of the invention may be applied to any pre-terminfants, preterm infants having gestational ages of 32 weeks or less andparticularly 30 weeks or less may benefit particularly from theinventive apparatus and methods described herein.

One example aspect of the invention provides apparatus for treatingpremature infants. The apparatus comprises an incubator housing, awarming system comprising a temperature controller connected to controla temperature within the incubator housing and a humidifier connected tomaintain a desired humidity level within the incubator housing. Aplatform is provided within the housing. The platform dimensioned tosupport an infant. One or more actuators are connected to the platformand are operable to move the platform in at least a vertical directionwith an oscillating motion. A controller is connected to control theactuators to move the platform to oscillate in the vertical direction ata frequency in the range of 5 to 25 oscillations per minute. Theplatform may have a flat unobstructed top surface.

Another example aspect provides apparatus for treating prematureinfants. The apparatus comprises a premature infant incubator comprisinga platform within a housing of the premature infant incubator. Theplatform is dimensioned to support an infant on a substantially planarupper surface. An actuation system is connected to drive motion of theplatform in at least a vertical direction with an oscillating motion. Acontroller is connected to control the actuation system to move theplatform to oscillate in the vertical direction at a frequency in therange of 5 to 25 oscillations per minute.

Another example aspect provides apparatus for treating prematureinfants. The apparatus comprises a platform insertable into a housing ofa premature infant incubator and dimensioned to support an infant on asubstantially planar upper surface. An actuation system is connected todrive motion of the platform in at least a vertical direction with anoscillating motion. A controller is connected to control the actuationsystem to move the platform to oscillate in the vertical direction at afrequency in the range of 5 to 25 oscillations per minute.

Apparatus according to any of the above example embodiments as well asother embodiments described herein may provide various additionalfeatures individually or in any combinations. The following paragraphssummarize some such features.

Various options may be provided for controlling operation of theplatform. For example apparatus may provide one or more of the followingfeatures:

-   -   In some embodiments the apparatus comprises a control which is        operable by a user to adjust the frequency of the oscillations        of the platform.    -   In some embodiments the apparatus comprises a blood oxygen        sensor connected to supply a blood-oxygen signal representing        blood oxygen content to the controller and the controller is        configured to adjust one or both of a frequency and amplitude of        oscillation of the platform based on the blood-oxygen signal.    -   In some embodiments the apparatus comprises a heart monitor        associated with a signal processor configured to process an        output signal of the heart monitor signal to yield a HRV signal        indicative of heart rate variability wherein the controller is        configured to adjust one or both of a frequency and amplitude of        oscillation of the platform based on the HRV signal.    -   In some embodiments the controller comprises a stored schedule        of pain events and the controller is configured to initiate        oscillation of the platform in coordination with pain events in        the schedule of pain events.

The upper surface of the platform may have features that provide askin-like interface. For example:

-   -   an upper surface of the platform may comprise a breathable        waterproof material such as a flexible EPTFE membrane.    -   the upper surface of the platform may be characterized by a        durometer on the Shore OO scale.    -   a layer of a low durometer material may underlie the breathable        waterproof material.

The platform may be controllable to provide levels of displacementand/or acceleration to the infant sufficient to provide beneficialreductions in pain and/or reductions in sub-baseline blood oxygen levelfluctuations. In some embodiments:

-   -   the oscillations of the platform have a total vertical        displacement in the range of 1 mm to 5 cm at least at a location        of the infant's head.    -   the oscillations of the platform have a total vertical        displacement in the range of 1mm to 5 cm at a geometric center        of the platform.    -   the oscillations of the platform have a total vertical        displacement in the range of ½ to 2 cm at least at a location of        the infant's head.    -   the oscillations of the platform have a total vertical        displacement in the range of ½ to 2 cm at the geometric center        of the platform.

The platform may be constructed so that it is stiff and provides a flatsurface for supporting the infant. For example:

-   -   the platform may comprise a stiff generally planar form. The        form may, for example, comprise an acrylic material. The acrylic        material may be vacuum formed.    -   the platform may be formed with a peripheral skirt which may        stiffen the platform.

The apparatus may comprise a sound and vibration transducer. In suchembodiments the controller may comprise a memory storing pre-recordeddigitized heartbeat sounds or a sound generator configured to generatesimulated heartbeat sounds. The controller is connected to drive thesound and vibration transducer with the recorded heartbeat sounds fromthe memory or the simulated heartbeat sounds from the sound generator.The sound and vibration transducer may be mounted to the platform (e.g.under the platform).

The platform and/or incubator housing may include features to facilitateX-ray imaging or other forms of imaging of the infant. For example,apparatus may have one or more of the following features:

-   -   the platform is X-ray transparent.    -   indicia on a top surface of the platform indicates an area of an        X-ray transparent portion of the platform.    -   a compartment provided under the platform is dimensioned to        receive an X-ray film cartridge or a digital X-ray image sensor.        The compartment may comprise, for example, a pull-out drawer or        a slot.

Various arrangements may be provided to drive the platform. Preferablythe system for driving the platform operates quietly (e.g. such that asound level at the location of the infant does not exceed 60 dB). Insome example arrangements:

-   -   one or more actuators are connected directly between the        incubator housing and the platform.    -   the platform is suspended relative to the incubator housing by a        bias mechanism (which may, for example, comprise one or more        springs) and one or more actuators are operable to displace the        platform upwardly and downwardly relative to an equilibrium        position of the platform.    -   one end of the platform may be pivotally mounted for rotation        about a pivot axis and one or more actuators may be connected to        rotate the platform about the pivot axis.    -   actuators may be connected to lift and lower the platform while        preserving an orientation of the top surface of the platform.    -   one or more actuators may be located in all or in part outside        of an incubator housing and may be connected to move the        platform within the incubator housing.    -   the platform may be mounted to an incubator housing and the one        or more actuators may be connected to oscillate the incubator        housing and the platform in the vertical direction. In such        embodiments the platform may be fixedly mounted to the incubator        housing.

Another example aspect provides use of apparatus as described herein forcontrolling pain in preterm infants and/or for reducing sub-baselinefluctuations of brain blood oxygen associated with a scheduled painevent in preterm infants.

Another example embodiment provides a method for treating a preterminfant, The method comprises placing the infant on a platform; prior toa pain event commencing moving the platform to oscillate substantiallyvertically at a frequency in the range of 5 to 25 oscillations perminute; and continuing vertically oscillating the platform after thepain event.

Another example embodiment provides a method for controlling pain in apreterm infant, The method comprises: prior to a scheduled pain event,placing the preterm infant on a platform and commencing moving at leastthe infant's head substantially vertically by reciprocating the platformat a frequency in the range of 5 to 25 oscillations per minute;subjecting the infant to the pain event; and continuing verticallyoscillating the platform after the pain event at a frequency in therange of 5 to 25 oscillations per minute, the oscillations before andafter the pain event having an amplitude sufficient to cause in theinfant a reduction in stress as demonstrated by an increase in heartrate variability of the infant.

Another example embodiment provides a method for reducing sub-baselinefluctuations of brain blood oxygen concentration in a preterm infant.The method comprises: prior to a scheduled pain event, placing thepreterm infant on a platform and commencing moving at least the infant'shead substantially vertically by reciprocating the platform at afrequency in the range of 5 to 25 oscillations per minute; subjectingthe infant to the pain event; and continuing vertically oscillating theplatform after the pain event at a frequency in the range of 5 to 25oscillations per minute. The oscillations before and after the painevent have an amplitude sufficient to cause in the infant a reduction insub-baseline fluctuations of brain blood oxygen concentration asdemonstrated by non-invasive transcranial NIRS measurements of the bloodoxygen concentration in the infant's brain.

Methods according to any of the above example embodiments as well asother embodiments described herein may provide various additionalfeatures individually or in any combinations. The following paragraphssummarize some such features.

The methods may be performed on preterm infants at various gestationalages. Some particular benefits may be achieved where the infant has agestational age of not more than 32 weeks or not more than 30 weeks. Insome embodiments the infant has a weight of 1500 g or less or a weightof 1200 g or less.

The oscillations may have levels of displacement and/or accelerationsufficient to provide beneficial reductions in pain and/or reductions insub-baseline blood oxygen level fluctuations. In some embodiments:

-   -   the oscillations have a total vertical displacement in the range        of 1 mm to 5 cm at least at a location of the infant's head.    -   the oscillations have a total vertical displacement in the range        of 1 mm to 5 cm at a geometric center of the platform.    -   the oscillations have a total vertical displacement in the range        of ½ to 2 cm at least at a location of the infant's head.    -   the oscillations have a total vertical displacement in the range        of ½ to 2 cm at the geometric center of the platform.

The oscillations may be performed at least in time periods before and/orafter the pain event. For example, for at least 15 minutes before thepain event and/or for at least 5 minutes after the pain event. In someembodiments the oscillations are maintained substantially continuouslyfor extended periods of time (hours or days) during which a number ofpain events may occur. In some embodiments oscillation and/or deliveryof heart sounds is provided for at least 9 or 10 hours of a 12-hourperiod.

Various options may be provided for controlling stimulation of theinfant by oscillations and/or sounds. For example methods may provideone or more of the following features:

-   -   In some embodiments the methods set frequency and/or amplitude        of the oscillation based on receiving an input at a control.    -   In some embodiments the methods comprise setting one or both of        a frequency and amplitude of the oscillation based on a        blood-oxygen signal.    -   In some embodiments the methods comprise setting one or both of        a frequency and amplitude of the oscillation based on a HRV        signal.    -   In some embodiments the methods comprise setting one or more of        a frequency, character and amplitude of heartbeat sounds based        on a HRV signal.    -   In some embodiments the methods comprise setting one or more of        a frequency, character and amplitude of heartbeat sounds based        on a measure of blood oxygen level in the infant.    -   In some embodiments the methods control the oscillation based on        a stored schedule of pain events. for example, oscillation may        be automatically initiated in advance of a scheduled pain event        such as a blood test.

In some embodiments the methods may include performing a positioningprotocol on the infant. The positioning protocol may comprisepositioning the infant in supine, sidelying and prone positions on theplatform.

Further aspects and example embodiments are illustrated in theaccompanying drawings and/or described in the following description.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a partially schematic side elevation view of an incubatoraccording to an example embodiment of the invention.

FIG. 2 is a flow chart illustrating a method according to an exampleembodiment.

FIG. 3 is a plot illustrating brain blood oxygen concentrationfluctuations in infants subjected to heel pricks for blood collection.

FIG. 4 is a block diagram of a control system according to an exampleembodiment comprising an ECG system and a blood oxygen monitor.

FIG. 5 is a photograph showing an example platform form in an incubator.The surface coverings have been removed from the form in thisphotograph.

DETAILED DESCRIPTION

Throughout the following description, specific details are set forth inorder to provide a more thorough understanding of the invention.However, the invention may be practiced without these particulars. Inother instances, well known elements have not been shown or described indetail to avoid unnecessarily obscuring the invention. Accordingly, thespecification and drawings are to be regarded in an illustrative, ratherthan a restrictive sense.

This invention has a number of aspects. One aspect provides incubatorsfor preterm infants. An incubator is fitted with apparatus for providingsensations to a premature infant. The sensations include rising andfalling motion similar to what an infant would experience lying on hisor her mother's chest as the mother breathes naturally. The inventorshave discovered that use of apparatus which provides such sensations canreduce the responses of premature infants to pain, as well as tostabilize blood oxygen levels (particularly brain blood oxygen levels)in premature infants.

Another aspect of the invention provides apparatus for providingsensations to premature infants. The apparatus may be placed inside aneonatal intensive care incubator. Another aspect of the inventionprovides methods for treating premature infants, especially very orextremely premature infants, to reduce pain response, reduce stress,and/or improve the uniformity of brain blood oxygen concentration.

FIG. 1 illustrates an example incubator 10. Incubator 10 may have arange of features that are common or standard in NICU incubators. In theillustrated embodiment incubator 10 comprises a housing 12. Atemperature and humidity control system 14 maintains desired temperatureand humidity levels within housing 12. Doors 15 are provided tofacilitate access to an infant B lying within housing 12. An air supplytube 17 may carry air having a regulated oxygen content to infant B froma ventilator, continuous positive airway pressure (CPAP) machine, oroxygen supply.

Baby B lies on a surface 21 of a platform 20. Surface 21 provides asimulated skin interface that allows for transpiration of moisture (e.g.sweat) of the baby B. Surface 21 mimics the interfacial feel of humanskin. Surface 21 may be embodied, for example, by a low durometer (verysoft) material disposed above a stiff form made, for example, ofacrylic. An example form is shown in FIG. 5. The FIG. 5 embodimentincludes a skirt extending around a periphery of the form.

The durometer of the material of surface 21 may, for example, bemeasured on the Shore OO scale. The measurement may be made according tothe ASTM D2240-00 testing standard. The OO scale measures the softnessof materials that are indented in the range of up to 0.1 inches (2.54mm) by a spherical indenter having a radius of 1.20 mm under an appliedforce of 1.11 Newtons (113 grams force).

In some embodiments platform 20 comprises a stiff vacuum-formed acrylicshell. The shell is predominantly flat in at least the area thatsupports infant B in normal use. Providing a flat and open area forsupporting an infant B is advantageous for facilitating positioningprotocols to be performed on infant B as discussed below. All materialsused in apparatus 10 should be fully cured before use and selected toavoid materials that release gases (e.g. by off-gassing) that could beharmful to infant B.

Examples of materials that may be used to provide surface 21 include:silicone rubber, “memory foam” (e.g. viscoelastic polyurethane),sorbothane, natural rubber, and other similar sterilizable elasticpolymers. The materials of surface 21 preferably do not affect X-rayssignificantly. At least some gels can significantly absorb X-rays.Surface 21 preferably does not include such gels at least in the portionof platform 20 that supports infant B in normal use. A layer of suchmaterial may be covered with a breathable covering to provide surface21. For example, in some embodiments, surface 21 comprises a softmaterial covered by a breathable synthetic cloth. The cloth may, forexample be a nylon cloth. In some embodiments the cloth is coated with abreathable but liquid-blocking material such as EPTFE (expandedpolytetrafluoroethylene). EPTFE is soft, flexible and porous. EPTFE ispermeable to air, yet watertight at low pressures.

Platform 20 is movable by one or more actuators 22 which operate undercontrol of a controller 26. These motions are transferred to infant Bwho is supported on platform 20. Actuators 22 may be controlled to moveplatform 20 to effect a simulated maternal breathing motion. Forexample, platform 20 may be oscillated in a substantially verticalmanner, at a frequency in the range of 5 to 25 oscillations per minute,preferably 10 to 18 oscillations per minute. Depending on how platform20 is actuated, the displacement of the platform may be uniform at alllocations on the platform or may vary from place-to-place on theplatform. Displacement, of platform 20 at the position of the infant'shead may, for example, be in the range of 0.1 to 5 cm. Preferably, therange of motion of platform 20 in the vertical direction at the positionof the infant's head is in the range of 0.5 to 2 cm.

The oscillating motion of platform 20 may optionally include a shortdwell at either or both of the maximum and minimum displacements ofplatform 20. In some embodiments position and/or velocity of platform 20are controlled by a servo controller. In some embodiments, accelerationof platform 20 is controlled such that acceleration of platform 20smoothly increases and decreases during the oscillation. In someembodiments the oscillating motion of platform 20 is sinusoidal orapproximately sinusoidal. In some embodiments acceleration of platform20 is limited to a value not exceeding about 0.4 in/sec² (about 1cm/sec²).

Such an oscillating motion applies a periodic acceleration to theinfant. Where the imparted motion is sinusoidal or nearly so the maximumvelocity, v_(max), is given by v_(max)=2πDf where D is the displacementamplitude (½ of the total displacement of the platform) and f is thefrequency. In the above examples, v_(max) is in the range of 2π×0.1cm×½×5 min⁻¹=1.57 cm/min to 2π×5 cm×½×25 min⁻¹=392 cm/min with apreferred range of 15.7 cm/min to 113 cm/min. The maximum acceleration,a_(max), is given by v_(max)=D(2πf)² which, for the above examples is inthe range of 100 cm/min² to 123000 cm/min² with a preferred range ofabout 2000 cm/min² (about ½ cm/sec²) to about 25500 cm/min² (about 7cm/sec²).

Actuators 22 may be of any suitable type or types. Actuators 22 maydrive different types of mechanical motion, may be powered by differentpower sources and/or may generate motion according to different physicalprinciples and/or mechanical arrangements. For example, actuators 22 maycomprise linear actuators, rotary actuators, or pivoting actuators.Actuators 22 may be powered by electricity (e.g. linear actuators,electric motors, servo motors), pressurized gas (e.g. pneumaticcylinders, inflatable bladders, pneumatic motors) or pressurized fluid(e.g. hydraulic cylinders or hydraulic motors). Actuators 22 maydirectly move platform 20 to rise and fall or may be coupled to moveplatform 20 using any suitable linkages. Examples of linkages includescrews, rack and pinion mechanisms, pivoting links, and/or crankmechanisms.

Actuators 22 may be selected to be compatible with the environment of anintensive care nursery. Preferably, actuators 22 operate quietly suchthat the total sound level within incubator 10 does not exceedapproximately 60 decibels. Sounds louder than this can harm hearing inpremature infants (see e.g. Graven, 2000 J Perinatol. 2000 December;20(8 Pt 2):588-93). Electrical actuators and controls, if used, maysatisfy requirements for limited emissions of electromagneticinterference.

In some embodiments a plurality of actuators 22 are operated in concertto raise and lower platform 20. For example, three or more actuators 22may be spaced apart around a periphery of platform 20. The actuators 22may be extended and retracted together to cause platform 20 to rise andfall as described above.

In an alternative embodiment, platform 20 is pivotally mounted forrotational movement about a horizontal axis near one end of platform 20.In such embodiments the infant would typically be oriented such that hisor her feet are toward the pivoting end of the platform. One or moreactuators 22 may be operated to pivot platform 22 about the horizontalaxis with the result that the other end of platform 20 moves with thedesired substantially-vertical motion at the nominal position where aninfant's head would be placed.

In some embodiments (including embodiments with any of the aboveactuator arrangements) platform 20 is supported by a bias mechanismwhich may comprise, for example, one or more springs such that actuators22 drive platform 20 both up and down from an equilibrium position. Thebias mechanism may be set such that platform 20 settles at a desiredaverage height when carrying an infant weighing, for example, 1.5 kg. Insome embodiments the bias mechanism is adjustable to fine tune theequilibrium positions for different infants. Where the weight ofplatform 20 and infant B is primarily supported by such a bias mechanismthe mechanical work performed by actuators 22 and the forces exerted byactuators 22 in oscillating platform 20 may be reduced. These factorsmay, in turn, reduce the amount of heat dissipated by actuators 22and/or the noise made by actuators 22 as well as improve the energyefficiency of the apparatus.

In some embodiments, platform 20 is arranged to prevent fluids that maybe present in the vicinity of infant B from entering the space belowplatform 20. For example, platform 20 may be shaped to form a rim aroundits edges. Any such shaping should preferably avoid a configurationwhich can trap CO₂ in the vicinity of the infant's head. CO₂ canadversely affect breathing rate and drive to breathe.

In some embodiments platform 20 is arranged so that it is tilted. Insome embodiments a degree of tilt of platform 20 is adjustable eitherstepwise or continuously. Platform 20 may comprise a drain located in anarea that is low when the platform is tilted.

In some embodiments the clearance between platform 20 and incubatorshell 12 is such that there are no pinch points between platform 20 andincubator shell 12. This may be achieved by providing either a verysmall clearance or a large enough clearance. For example, in someembodiments the clearance between platform 20 and incubator housing 12is approximately 1 cm, which is generally large enough to avoidpinching. Such a gap is also large enough to allow air to flow asplatform 20 is oscillated.

In some embodiments a flexible bellows extends between platform 20 andincubator shell 12 and/or a surround of platform 20 is attached to movetogether with platform 20 such that there is no pinch space around theperiphery of platform 20 that could pinch any part of the infant B orequipment such as ventilator tubes, ECG electrode wires, IV tubes or thelike. The flexible bellows, if present, is optionally a continuation ofa cover of platform 20. These constructions may also be advantageous forattenuating sounds from actuators 22 or other mechanisms under 20 at thelocation of infant B on top of platform 20. In embodiments where thereis little clearance between platform 20 and incubator housing 12 and/ora bellows or the like impedes airflow around platform 20 thenalternative vents or openings ay be provided to allow for airflow intoand out of the space below platform as platform 20 is moved.

Positioning of a preterm infant has important musculoskeletalimplications. Skeletal structures are highly plastic and responsive tobody positioning such that movements and postures received or imposed inthe NICU contribute to the shaping of the infant's body, joints andskull. It is desirable to apply positioning programs to provide forproper development. Such positioning programs may include positioningthe infant in supine, sidelying and prone positions, each with specificaims for musculoskeletal development (See: Jane Sweeney,“Musculoskeletal Implications of Preterm Infant Positioning in theNICU”, Journal of Perinatal and Neonatal Nursing, Apr. 23, 2002).Platform 20 may be configured to facilitate such positioning. In theillustrated embodiment, platform 20 is large enough to position apreterm infant in any of the above postures and is free of obstaclesthat would obstruct NICU caregivers from providing such positioningprograms.

In the illustrated embodiment, a sound and/or vibration transducer, suchas a speaker 24, is provided in incubator 10. For example speaker 24 maybe mounted on platform 20 to convey sounds and vibrations directly to aninfant lying on surface 21. Speaker 24 may be controlled to emit soundsand vibrations which are reminiscent of the intrauterine environment.For example, speaker 24 may be controlled to emit recorded or simulatedheartbeat sounds. Controller 26 may include a memory storing apre-recorded heartbeat sounds and/or a heartbeat simulator thatsynthesizes sounds having the periodicity and timbre like those ofheartbeat sounds (as present in the intrauterine environment).

Platform 20 may optionally provide one or more additional features suchas:

-   -   an adjustable tilt so that medical caregivers may adjust the        height of one end of platform 20 to facilitate easier breathing        by the infant (e.g. tilt the platform such that the infant's        head is higher than his or her feet). Such a tilting mechanism        may be provided by a mechanism arranged to adjust and fix the        height of one end of the platform (e.g. a ratchet, cam-lock,        screw, movable block, wedge, hook etc.). an opposing end of        platform 20 (preferably the foot end) may be hinged.    -   a lock to hold platform 20 against moving. The lock may be        engaged to create a solid backing surface for the infant if        caregivers must perform cardio-pulmonary resuscitation (CPR). In        some embodiments the lock is integrated with a drive mechanism        that actuates oscillation of platform 20. For example the lock        may be implemented by electrically holding an electric motor        that actuates the drive mechanism, actuating a brake in the        drive mechanism, closing a valve to hold actuators of a        hydraulic drive mechanism in a current position or the like. In        other embodiments a mechanical lock is provided. In some        embodiments, pressing down on platform 20 with more than a        threshold amount of force locks platform 20 in place. The same        action may disable operation of the actuators that drive motion        of platform 20. For example, if platform 20 is pressed down        firmly spring-loaded catches may automatically engage between        platform 20 and incubator housing 12 to lock platform 20 in        place. At the same time a micro switch, optical sensor or the        like may sense that platform 20 has been locked and signal        controller 26 to inhibit oscillation of platform 20.    -   a load cell or pressure sensor arranged to measure a weight of        an infant on platform 20.    -   markings to assist in positioning infant B. For example,        platform 20 may be marked to indicate a ‘normal’ position for an        infant, a desired location of the infant's head, the extent of        an area of platform 20 that is X-ray transparent and/or suitable        for other medical imaging modalities and/or a location of        speaker 24. It may be desirable to place the infant's head close        to but not directly on top of speaker 24.    -   markers for use in medical diagnostics (e.g. a ruler and/or one        or more markings visible in X-ray images).

Controller 26 includes a user interface 27 which allows a user to alteroperating parameters used by controller 26. For example, interface 27may provide controls that allow a user to adjust the rate at whichplatform 24 is moved to simulate breathing (i.e. a rate of oscillationof platform 20). Other controllable parameters may include one or moreof the amplitude of motions of platform 20, the pattern of motion ofplatform 20 (e.g. does platform 20 merely move up and down in a verticalmotion or is it optionally also rocked from side-to-side or head totoe), heartbeat sound, amplitude, and frequency delivered by speaker 24.

User interface 27 may additionally include controls that allow acaregiver to enable operation of the apparatus in advance of a ‘stress’(or pain) event for infant B (e.g. by setting a timer to turn onoscillation of platform 20 at a certain time and/or for a certainduration). In some embodiments user interface 27 optionally providescontrols which enable and/or set parameters for automatic control ofapparatus 10 in response to measurements of physiological conditions ofinfant B. Such automatic control may incorporate a feedback mechanismusing as an input physiological parameters that may comprise, forexample, one or more of HRV and blood oxygen concentration.

In the illustrated embodiment, a data store 28 contains parameters 29which may include parameters set by a user by way of user interface 27and/or other parameters that affect the operation of incubator 10.

Preterm infants may be highly fragile, especially those who are very orextremely premature, and may require diagnostic imaging tests such asX-rays. Incubator 10 may be designed such that lift mechanisms (e.g.actuators 22 and any linkages) are located peripherally in incubator 10.Platform 20 may be substantially transparent to X-rays (e.g. thematerials of which platform 20 is constructed may be chosen to haveradio-transparency sufficient to enable imaging radiation, such asX-rays, to pass through without adversely affecting X-ray images.Further, at least the area of platform 20 which supports infant B ispreferably uniform and planar to minimize any distortion of X-ray imagesby platform 20.

In some embodiments a compartment 30 (e.g. a space or drawer) isprovided between the bottom of incubator 10 and platform 20. Compartment30 may be dimensioned to receive image-receiving plates, such as adigital X-ray sensor or a cartridge holding X-ray film. With thisarrangement, diagnostic images of an infant on platform 20 may be takenwithout requiring the infant to be removed from incubator 10. The top ofincubator housing 12 may include an X-ray transparent and non-distortingwindow (e.g. a planar portion of the incubator housing) such that thehead of an X-ray machine may be positioned above and outside incubator10 to image infant B. In some embodiments incubator 10 includes acompartment or slot into which an image-receiving plate may be insertedvertically for the purpose of obtaining lateral X-rays of infant B. Insuch embodiments X-rays may be delivered laterally through an openporthole in incubator housing 12. Motion of platform 20 may bediscontinued while X-rays are being taken.

Platform 20, and its associated mechanisms, may be tightly integrated inthe construction of incubator 10. For example, actuators 22 may beattached to housing 12 of incubator 10, platform 20 may replace and/orbe integrated with bottom plate of incubator 10. In some embodimentsactuators 22 cause an entire incubator housing within which infant B islocated to oscillate vertically. In such embodiments platform 20 may befixed to the oscillating incubator housing. This construction may haveone or more advantages such as:

-   -   eliminating any problems that could result from gaps between a        moving platform and a fixed incubator housing,    -   providing improved isolation of infant B from sounds made by        actuator(s) 22,    -   cost-effective construction,    -   improved control of the airflow within the incubator/environment        surrounding the infant.    -   easy cleaning.

In some embodiments, controller 26 is integrated with controllers forother functions of an incubator. For example, controller 26 may providea single interface which allows a user to control overall operation ofan incubator including temperature, humidity, motion of platform 20, andsounds/vibrations delivered to an infant.

In alternative embodiments, platform 20, and its associated mechanism,is provided as a stand-alone device that may be placed inside apre-existing neonatal incubator. Where platform 20 and its associatedmechanisms are designed to be used with an existing neonatal incubatorit is generally preferred that platform 20 and its associated mechanismhave a thickness of about 7 cm or less above the top of the incubatorbottom plate (with platform 20 at the low-point in its movement). Mostexisting incubators have dimensions ample enough to accept apparatus ofabout 7 to 8 cm in thickness without imposing ergonomic constraints onmedical staff/parents reaching through portholes of the incubator tocare for the infant when the platform is stationary or in motion.

The inventors have discovered that stimulation, as provided by apparatus10, can significantly reduce the stress level of premature infants. Suchstimulation can also provide very significant reduction in thesensitivity of the infants to pain. By providing such stimuli, adverseeffects of painful events such as pricks to remove blood for testing maybe reduced. These benefits are achieved in premature infants born at agestational age of 36 weeks or less. These benefits may be particularlyimportant for premature infants born at a gestational age of 30 weeks orless.

A pilot clinical trial of a prototype apparatus that provided stimuli asdescribed above (e.g. vertical oscillation at a frequency typical ofbreathing in an adult human, sounds and vibrations typical of theheartbeat of an adult human and interfacial contact with a surfacesimilar to human skin) showed that the physiological pain response ofpreterm infants exposed to such stimuli is significantly reduced whencompared to the current standard of care, both in length and severity.In a method according to an example embodiment a preterm infant (havinga gestational age of 36 weeks or less), in some embodiments an infanthaving a gestational age of 30 weeks or less, is positioned on platform20 before, during and after an event that may cause pain to the infant,such a blood sampling from a heel prick. The current standard of care tomitigate such pain is for a nurse (or parent) to provide facilitatedtucking, which can be described as holding the infant in the arms of thenurse and providing moderate constraining pressure upon the infantduring and for a short time immediately after the pain event.

A pilot study of 9 preterm infants with a mean gestational age of 29weeks and mean age of 25 days, was conducted during routine bloodcollection procedures. The infants were randomly selected to be in acontrol group who received facilitated tucking or a test group whoreceived stimulation by way of the prototype device (simulated maternalsimulation).

Heart rate variability (HRV) was measured for each of the infants duringeach of a plurality of periods. A baseline period, a heel prick periodand a recovery period. Baseline period is the two-minute period directlypreceding the skin breaking for the blood test. Heel prick period is thetwo-minute period directly after the skin breaking for the blood test.Recovery period is the two-minute period directly after the last contactby the lab technician who completed the blood test. The person whoselected these data for analysis did not know what treatment group theHRV data came from so as to avoid bias during the analyses.

HRV provides a measure of stress. HRV is calculated by measuringmultiple values of the inter-beat interval heart (the interval betweenconsecutive beats of a person's heart) over a test interval and applyinga mathematical operation to these values. The inter-beat interval of aperson's heart can vary widely and an accepted measure of this is HRV.In particular, researchers have found, using frequency domain methods(e.g., Fast Fourier Transform), that the power within frequency bands ofthe HRV can be used to determine stress.

For this study, power spectral estimates of HRV were quantified usingthe area (power) of the spectrum in a high frequency region of the HRVspectrum (0.15-0.80 Hz region for neonates). HRV may be measured inmilli-seconds squared per Hertz. HRV HF power is generally considered tobe a direct measure of parasympathetic (PS) nervous system activationand is inversely proportional to stress.

The heart rate signals were recorded using a single-lead surface ECG(lead II) (Biopac, Ca.). Continuous ECG signals were digitally sampledat 360 Hz using a specially adapted portable computer system. Customphysiological signal processing software (Mindware, USA) was used toacquire, process and analyze the data. HRV data was acquired in 2-minuteblocks before, during and after blood collection.

As noted above, HRV serves as a direct measure of parasympatheticactivation. During a baseline period (prior to heel prick), infants onthe prototype device had 88% better parasympathetic activation (wereless stressed) as indicated by the higher HF HRV values than infants inthe Control group. In addition, PS activation (stress reduction) at thetime a blood was taken by a heel prick was 43% greater for infants onthe prototype device than for infants in the control group. During therecovery period, PS activation was 73% better for infants on theprototype device than for infants in the control group. These findingsdemonstrate that a method which involves delivering stimuli to prematureinfants as described herein is effective for pain and stress reductionin the infants, particularly surrounding painful events.

Table 1 provides a summary of the pilot test data.

TABLE 1 Results of Pilot Trial using Invented Devices vs. standard ofcare: Heart Rate Variability - High Frequency Power HRV: HF Power(ms²/Hz) Baseline Heel Prick Recovery Control Mean 5.82 2.02 3.73(N =3)* Group 1 (N = 4) Invented Device Mean 45.84 3.56 13.82 Group 2 (N =5) Difference 40.01 1.54 10.09 •One infant with significant outlier dataremoved.

In one version of the prototype device, movement of the platform wascaused by a pneumatic drive mechanism. The pneumatic drive mechanismprovided the lifting forces required to simulate maternal breathing. Thepneumatic drive system included a source of pressurized gas, a system ofcontrol valves, and pneumatic lift pistons located within an incubator.The control valves were operated to cause the lift pistons toreciprocate the platform up and down in a generally vertical direction.This is one example of a case where power for actuating movement ofplatform 20 is provided and controlled from outside of incubator 10.Another version of the prototype device provided a rotary motorconnected to drive two shafts synchronized to rotate together by meansof a toothed belt. Each of the shafts drove rotation of a cam whichcaused the platform to move vertically. The rotary motor was locatedoutside the incubator and the motion was transmitted to the shafts via acable, such as one commonly used for steering mechanisms. The platformin the prototype devices has a height of 6.5 cm, a width of 35.5 cm, anda length of 56 cm

FIG. 2 illustrates a method 40 according to an example embodiment of theinvention. Method 40 stimulates a preterm infant with stimulations whichsimulate maternal breathing, skin-to-skin interface, and maternalheartbeat.

Method 40 begins by selecting a preterm infant in block 42. In someembodiments the infant has a gestational age of not more than 32 weeksand/or a weight of less than 1500 grams. In block 44, the infant isplaced in a platform (such as platform 20 of incubator 10).

In block 45 the platform is operated as described above. The infant'sskin is in contact with a material on the upper surface 21 of platform20 which simulates the feel of maternal skin. Platform 20 is driven toreciprocate up and down at a tempo reminiscent of maternal breathing(e.g. at a frequency in the range of 5 to 25 oscillations per minute,preferably 10 to 18 oscillations per minute with a displacement at leastat the position of the infant's head in the range of 0.1 to 5 cm,preferably 0.5 to 2 cm). The infant's head is typically centered on theplatform about 14 cm from the edge of one end of the platform (nominallythe ‘head end’) while the platform is being oscillated.

Optionally, sounds and vibration are transmitted to the infant by way ofspeaker 24 at a frequency or frequencies characteristic of the maternalheartbeat. Oscillation of platform 20 is preferably commenced at least15 minutes before a pain event. Platform 20 may be oscillatedcontinuously for extended periods.

In block 46, the infant is subjected to a pain event, such as a prickfor drawing blood for tests. In block 48, stimulation of the infant iscontinued as in block 45. Oscillation of platform 20 is preferablycontinued for at least 5 minutes after a pain event.

Without being bound to any particular theory regarding why method 40 iseffective, the inventors consider that method 40 may additionally helpto regulate breathing rates in preterm infants thereby reducing periodicbreathing (apnea), a condition associated with reduced oxygen levels inpremature neonates. In addition, by increasing parasympathetic heartrate variability method 40 may increase acetylcholine (a keyneurotransmitter secreted during parasympathetic heart rate regulation)which has a secondary anti-inflammatory effect.

Preterm infants are born with immature lungs and cannot provide adequateoxygenated blood to their organs. As a result, while in intensive care,they receive supplemental ventilation and oxygen. These treatmentsinduce inflammation in the lung tissue leading to a chronic lungcondition called bronchopulmonary dysplasia (BPD). Respiratory distressand BPD are the leading causes of death in premature neonates. Thus, anytreatment which reduces inflammation may reduce the risk of developingBDP and death. Method 40 may be effective to reduce inflammation throughstimulation of the parasympathetic system/increase in acetylcholine.

In addition to the above, the inventors have discovered that thebrain-blood-oxygen level in premature infants is highly variable duringand after a pain event, such as a routine blood sample collected from aheel-prick. Fluctuations in the blood oxygen level in the brain of apreterm infant can be significant, ranging from 20% above to almost 40%below baseline. Such fluctuations may last for an extended period oftime (e.g. 10 to 15 minutes). This places the infant at risk for eitherintracranial hemorrhage or anoxia, both of which can lead to short- andlong-term developmental issues for the infant.

This observation was made using a Near Infra-Red Spectroscopy (NIRS)machine with a prototype probe specifically designed in a small size foruse with premature infants. The probe was strapped in place over theinfants' scalps and provided direct measures of brain blood oxygenation.Brain blood oxygenated- and deoxygenated-hemoglobin concentrations([O2Hb], [HHb]), as well as two calculated values, total hemoglobinconcentrations at HIA=[O2Hb+HHb]) and local brain tissue saturation weremonitored in ten premature infants. The probe was positioned on eachinfant's skull to obtain direct brain blood measurements. Theseobservations indicated wide variations in blood oxygen during and aftera pain event. In one infant these changes persisted for 10 to 15minutes. In addition, results of the NIRS measurements correlated highlywith a valid and reliable behavioral pain scale (in this case theBehavioral Indicators of Infant Pain—“BIIP” scale).

Method 40 may be effective to reduce the magnitude and/or duration offluctuations of brain blood oxygen content below baseline that may becaused by pain events in premature infants. In general, the use ofapparatus as described herein may result in better brain-blood-oxygenstability for such infants while they reside in neonatal intensive careincubators. Improved brain-blood-oxygen stability would tend to improvedevelopmental outcomes for these infants, and should lead to a widerange of benefits for these infants, their parents, and significant costreduction for the health-care system. FIG. 3 is a graph comprisingcurves showing the incidence of sub-baseline brain blood oxygenationfluctuations for infants treated using the prototype device and infantsin a control group treated using the current standard of care.

Stimulation as described herein is optionally controlled based at leastin part on one or more of: a measure of stress in an infant (e.g. a HRVreading) and a measure of blood oxygen concentration, preferably ameasure of brain blood oxygen concentration. For example, FIG. 4 shows acontrol system according to an example embodiment comprising an ECGsystem 32 and a blood oxygen monitor 34. An output of ECG system 32 isprocessed in a signal processor 35 to yield a signal 37 indicative ofHRV. Signal processor 35 may, for example, comprise a filter or spectrumanalyzer that generates signal 37 based on the power within a highfrequency band of the HRV.

Controller 26 is connected to receive signal 37 and a signal 39representing blood oxygen content from blood oxygen monitor 34.Controller 26 is configured to adjust the intensity of stimulationprovided to the infant (e.g. to adjust one or more of the frequency ofvertical oscillation of platform 20, the amplitude of oscillation ofplatform 20, the and/or character of intensity of simulated heart soundsdelivered by speaker 24) based upon signals 37 and/or 39. The rate ofthe heart beat sounds and/or oscillations of platform 20 and/or theamplitude of heart beat sounds and/or oscillations of platform 20 may bealtered within a range of set parameters which set “safe” variability.Controller 26 may then increase or decrease rates in real time accordingto the infant's needs. For example if HRV indicates increasing stress orbrain blood oxygenation is decreasing below a threshold value or atabove a threshold rate then the intensity of stimulation (frequencyand/or amplitude) may be increased. Conversely, if the infant's HRVvalues indicate relatively low stress and satisfactory brain bloodoxygen content then the intensity of stimulation may automatically bedecreased. Controller 26 may optionally trigger warning or alarm signalsto caregivers in an NICU, based on HRV stress or blood oxygenmeasurements.

In some embodiments controller 26 comprises a timer and is configured toapply stimulation in a manner coordinated with a schedule for bloodtests or other pain events. For example, controller 26 may be configuredto actuate activation of platform 20 a predetermined time prior to ascheduled blood test and to continue the activation of platformoscillation for a predetermined time after the scheduled blood test.

Apparatus as described herein may be applied to transport incubators aswell as NICU incubators. Apparatus as described herein may beincorporated into a transport incubator. The opportunity to accessadvanced medical care as soon as possible after birth has a directimpact on mortality and morbidity of premature infants. The hourimmediately after birth of a premature infant may be considered a‘golden hour’ since effective treatment provided in that hour canmarkedly improve prospects for the premature infant, much in the sameway that prompt treatment of traumatic injuries in adults can lead tomarkedly better prospects for recovery.

A transport incubator allows safe transportation of premature infantsfrom outlying hospitals or clinics to urban medical centers in emergencysituations. A transport incubator has some specific technologicalrequirements and qualities that differ from incubators used in the NICU.These key requirements/qualities may include some or all of thefollowing:

-   -   Sturdier construction, capable of withstanding loads associated        with transport in ambulance, helicopter, aircraft or marine        rescue vessel    -   A self-contained, weather proof, independent power source to        provide power to life support and monitoring equipment.    -   Smaller size and lighter weight, suitable for carrying by two        emergency medical technicians    -   A suspension system that reduces vibration related to motion        (i.e., in airplanes, ambulances and helicopters).    -   An embedded life support and monitoring, comprising, for example        a ventilator, intravenous pumps, and oxygen delivery systems.    -   Protection from environmental noise.

Features of the various embodiments described herein may be mixed andmatched in any combinations or subcombinations to provide additionalembodiments. The embodiments described above are merely examples whichdemonstrate applications of the present technology. New embodiments maybe created, for example, by adding to any of the above-describedembodiment one or more features from one or more other describedembodiments. Other new embodiments may be created, for example, byreplacing one or more features of one described embodiment with one ormore features of other embodiments.

Interpretation of Terms

Unless the context clearly requires otherwise, throughout thedescription and the claims:

-   -   “comprise”, “comprising”, and the like are to be construed in an        inclusive sense, as opposed to an exclusive or exhaustive sense;        that is to say, in the sense of “including, but not limited to”;    -   “connected”, “coupled”, or any variant thereof, means any        connection or coupling, either direct or indirect, between two        or more elements; the coupling or connection between the        elements can be physical, logical, or a combination thereof;    -   “herein”, “above”, “below”, and words of similar import, when        used to describe this specification, shall refer to this        specification as a whole, and not to any particular portions of        this specification;    -   “or”, in reference to a list of two or more items, covers all of        the following interpretations of the word: any of the items in        the list, all of the items in the list, and any combination of        the items in the list;    -   the singular forms “a”, “an”, and “the” also include the meaning        of any appropriate plural forms.

Words that indicate directions such as “vertical”, “transverse”,“horizontal”, “upward”, “downward”, “forward”, “backward”, “inward”,“outward”, “vertical”, “transverse”, “left”, “right”, “front”, “back”,“top”, “bottom”, “below”, “above”, “under”, and the like, used in thisdescription and any accompanying claims (where present), depend on thespecific orientation of the apparatus described and illustrated. Thesubject matter described herein may assume various alternativeorientations. Accordingly, these directional terms are not strictlydefined and should not be interpreted narrowly.

“Premature infant incubator” means an incubator suitable for use as anincubator in a NICU or as a transportation incubator for a very orextremely premature infant. A premature infant incubator generally has asystem for maintaining temperature and humidity within desired ranges.

Controllers in embodiments of the invention may be implemented usingspecifically designed hardware, configurable hardware, programmable dataprocessors configured by the provision of software (which may optionallycomprise “firmware”) capable of executing on the data processors,special purpose computers or data processors that are specificallyprogrammed, configured, or constructed to perform one or more steps in amethod as explained in detail herein and/or combinations of two or moreof these. Examples of specifically designed hardware are: logiccircuits, application-specific integrated circuits (“ASICs”), largescale integrated circuits (“LSIs”), very large scale integrated circuits(“VLSIs”), and the like. Examples of configurable hardware are: one ormore programmable logic devices such as programmable array logic(“PALs”), programmable logic arrays (“PLAs”), and field programmablegate arrays (“FPGAs”)). Examples of programmable data processors are:microprocessors, digital signal processors (“DSPs”), embeddedprocessors, graphics processors, math co-processors, general purposecomputers, server computers, cloud computers, mainframe computers,computer workstations, and the like. For example, one or more dataprocessors in a control circuit for a device may implement methods asdescribed herein by executing software instructions in a program memoryaccessible to the processors.

While processes or blocks are presented in a given order, alternativeexamples may perform routines having steps, or employ systems havingblocks, in a different order, and some processes or blocks may bedeleted, moved, added, subdivided, combined, and/or modified to providealternative or subcombinations. Each of these processes or blocks may beimplemented in a variety of different ways. Also, while processes orblocks are at times shown as being performed in series, these processesor blocks may instead be performed in parallel, or may be performed atdifferent times.

In addition, while steps are at times shown as being performedsequentially, they may instead be performed simultaneously or indifferent sequences. It is therefore intended that the following claimsare interpreted to include all such variations as are within theirintended scope.

Some aspects of the invention may also be provided in the form of aprogram product. The program product may comprise any non-transitorymedium which carries a set of computer-readable instructions which, whenexecuted by a data processor in a control system for apparatus asdescribed herein cause the data processor to control the apparatus toexecute a method of the invention. For example, the data processor maycontrol an actuation system to cause a platform in an incubator to moveas described in any embodiment herein and/or to cause a sound/vibrationtransducer to deliver stimuli to an infant as described in anyembodiment herein. Program products according to the invention may be inany of a wide variety of forms. The program product may comprise, forexample, non-transitory media such as magnetic data storage mediaincluding floppy diskettes, hard disk drives, optical data storage mediaincluding CD ROMs, DVDs, electronic data storage media including ROMs,flash RAM, EPROMs, hardwired or preprogrammed chips (e.g., EEPROMsemiconductor chips), nanotechnology memory, or the like. Thecomputer-readable signals on the program product may optionally becompressed or encrypted.

Where a component (e.g. a software module, processor, assembly, device,circuit, etc.) is referred to above, unless otherwise indicated,reference to that component (including a reference to a “means”) shouldbe interpreted as including as equivalents of that component anycomponent which performs the function of the described component (i.e.,that is functionally equivalent), including components which are notstructurally equivalent to the disclosed structure which performs thefunction in the illustrated exemplary embodiments of the invention.

Specific examples of systems, methods and apparatus have been describedherein for purposes of illustration. These are only examples. Thetechnology provided herein can be applied to systems other than theexample systems described above. Many alterations, modifications,additions, omissions, and permutations are possible within the practiceof this invention. This invention includes variations on describedembodiments that would be apparent to the skilled addressee, includingvariations obtained by: replacing features, elements and/or acts withequivalent features, elements and/or acts; mixing and matching offeatures, elements and/or acts from different embodiments; combiningfeatures, elements and/or acts from embodiments as described herein withfeatures, elements and/or acts of other technology; and/or omittingcombining features, elements and/or acts from described embodiments.

It is therefore intended that the following appended claims and claimshereafter introduced are interpreted to include all such modifications,permutations, additions, omissions, and sub-combinations as mayreasonably be inferred. The scope of the claims should not be limited bythe preferred embodiments set forth in the examples, but should be giventhe broadest interpretation consistent with the description as a whole.

1.-154. (canceled)
 155. Apparatus for calming infants, the apparatuscomprising: a platform dimensioned to support an infant; one or moreactuators connected to the platform and operable to move the platform inat least a vertical direction with an oscillating motion; and acontroller connected to control the actuators to move the platform tooscillate in the vertical direction at a frequency in the range of 5 to25 oscillations per minute and at an amplitude of oscillation; at leastone sensor connected to provide an output signal to the controller, theat least one sensor comprising one or more sensors selected from: ablood oxygen sensor connected to supply a blood-oxygen signalrepresenting blood oxygen content to the controller wherein thecontroller is configured to control one or both of the frequency andamplitude of oscillation of the platform based on the blood-oxygensignal; and a heart monitor sensor associated with a signal processorconfigured to process an output signal of the heart monitor signal toyield a HRV signal indicative of heart rate variability wherein thecontroller is configured to control one or both of the frequency andamplitude of oscillation of the platform based on the HRV signal. 156.Apparatus according to claim 155 wherein the amplitude of theoscillations of the platform comprises a total vertical displacement inthe range of ½ to 2 cm at a geometric center of the platform.
 157. Theapparatus according to claim 155 wherein the at least one sensorcomprises the blood oxygen sensor.
 158. The apparatus according to claim157 wherein the blood oxygen sensor comprises a transcutaneous nearinfrared spectroscopy (NIRS) sensor.
 159. The apparatus according toclaim 157 wherein the controller is configured to adjust the amplitudeand/or frequency of the oscillations in response to the blood-oxygensignal representing a change in the blood oxygen content.
 160. Theapparatus according to claim 159 wherein the controller is configured toadjust a length of time during which the platform is moved to oscillatebased at least in part on the blood-oxygen signal.
 161. The apparatusaccording to claim 159 wherein the at least one sensor comprises theheart monitor sensor and the controller is configured to adjust theamplitude and/or frequency of the oscillations in response to a changein the heart rate variability indicated by the HRV signal.
 162. Theapparatus according to claim 161 wherein the controller is configured toadjust a length of time during which the platform is moved to oscillatebased at least in part on one or both of the blood-oxygen signal and theHRV signal.
 163. The Apparatus according to claim 160 wherein the heartmonitor comprises an ECG system.
 164. The apparatus according to claim155 wherein the at least one sensor comprises the heart monitor sensorand the controller is configured to adjust the amplitude and/orfrequency of the oscillations in response to a change in the heart ratevariability indicated by the HRV signal.
 165. The apparatus according toclaim 164 wherein the controller is configured to adjust a length oftime during which the platform is moved to oscillate based at least inpart on the blood-oxygen signal.
 166. The apparatus according to claim155 comprising a scheduler wherein the controller is configured toautomatically initiate moving the platform to oscillate in response toan event scheduled in the scheduler, wherein the controller isconfigured to control the one or more actuators to oscillate theplatform for a length of time following each pain event in the storedschedule of a plurality of pain events, wherein the length of time is atleast in part based on the HRV signal.
 167. The apparatus according toclaim 155 comprising user interface providing controls operative toreceive input from a user to alter operating parameters used bycontroller, the controls including at least a control operative toadjust the frequency of the oscillations.
 168. The apparatus accordingto claim 167 wherein the controls include a control operative to set apattern of the motion of the platform to combine vertical and rockingmotions.
 169. The apparatus according to claim 167 wherein the userinterface provides a control operative to set a timer to turn on theoscillation of the platform at a certain time and/or for a certainduration.
 170. The apparatus according to claim 155 wherein thecontroller is configured to monitor outputs of the at least one sensorand to trigger warning or alarm signals in response to the heart ratevariability indicated by the HRV signal or the or blood oxygen contentindicated by the blood-oxygen signal.
 171. The apparatus according toclaim 155 comprising a sound and vibration transducer wherein thecontroller comprises a memory storing pre-recorded digitized heartbeatsounds and the controller is connected to drive the sound and vibrationtransducer with the pre-recorded digitized heartbeat sounds from thememory.
 172. The apparatus according to claim 171 wherein the sound andvibration transducer is mounted to the platform.
 173. The apparatusaccording to claim 171 wherein the controller is configured to controlsounds delivered by the sound and vibration transducer based at least inpart on one or both of the HRV signal and the blood-oxygen signal. 174.The apparatus according to claim 155 comprising an incubator housingwherein the platform is contained within the incubator housing and theapparatus comprises systems for maintaining a set temperature andhumidity within the incubator housing.